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ONPS2388/1050 Immunology

A/Prof Peter Smooker,

peter.smooker@rmit.edu.au

Biotechnology and Environmental Biology,

Bundoora Campus

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ONPS2388/ONPS1050 ADVANCED IMMUNOLOGY AND CELL TECHNOLOGY

LECTURE SCHEDULE – 2009

Lectures: FRIDAY 9.30 am – 11.30 am in Room 207-03-2

Date WEEK T O P I C LECTURER 24 Jul 1 Outline of Course

Overview of the Immune System

Cells and Organs of the immune System

PS

31 Jul 2 Immune system receptors and receptor-antigen

interactions

PS

7 Aug 3 Antigen Processing and Presentation

JV

14 4 Co-stimulatory signals for T cell activation

PS

21 5 Cytokines as effectors: lymphocyte activation

Immunity to infection

PS

28 6 Allergy AL Semester Break

11 Sep 7 Immunoassays

MA

18 8 Antibodies and applications

Proteomics

AL

25 9 Approaches to vaccination

Immunotherapies

PS

2 Oct 10 Cancer immunology

TP

9 11 Transplantation immunology

RS

16 12 Immunological bioinformatics

PS

23 13 SwotVac

PS = A/Prof. Peter Smooker TP = A/Prof. Terry Piva AL = A/Prof. Andreas Lopata

JV = Dr. Jose Villadangos – Immunology Division, The Walter and Eliza Hall Institute,

villadangos@wehi.edu.au

MA = Dr. Mick Alderton - Immunologist, Senior Research Scientist, Combatant Protection and

Nutrition Branch, Defence Science and Technology Organisation Mick.Alderton@dsto.defence.gov.au

RS = Dr. Robyn Sutherland, Autoimmunity and Transplantation Division, The Walter and Eliza

Hall Institute, sutherland@wehi.edu.au

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Textbook

• Several lectures taken from Immunology6e

(Goldsby), others are lecturer’s own

material. PDF’s of the slides will be placed

on the Learning Hub

• A practical manual will be issued. Practical

classes run from weeks 3-4, 7-8, 9

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Assessment

• Three practical reports: 5% each

• Written report 35%

• Guidelines for written report will be given

out soon.

• End of year exam (2 hour): 50%

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Summary

• Bad guys get in

• Good guys (guards) recognise the bad guys

• Guards tell the army

• Army kills the bad guys

• Army sets up rapid response group

• Next time same bad guys get in, the rapid

response unit takes over

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Why do we need an Immune

system?

• We are surrounded by (and covered with!) a multitude of micro-organisms (viruses, bacteria and parasites)

• Some are harmful, many are not (some are beneficial)

• Which microorganisms can we live with?

• How do we contain these?

• How do we defeat pathogenic organisms?

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Example- TB infection

Tuberculous brochopneumonia,

left lung extensive bronchopneumoniaPrimary TB, infection has been

contained to a focus

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Pathogens

• An organism that produces disease in the

host is a pathogen

• These can be bacterial, viral or parasitic

• The majority of organisms associated with

the human body are bacterial

• Most are NOT pathogenic

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The good bugs- normal

microflora…

• Our surface tissues are colonised

• Skin (2 M2, 1012 bacteria). 2.5 million per

cm2

• Mucosal and other exposed tissues- includes

intestinal tract, urogenital tract, ear, eye etc.

• Largest community- colon. Up to 1012

bacteria per gram of faeces.

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Why haven’t we evolved to

eliminate these bacterial hordes?

Because they are beneficial to us!

• They out-compete pathogens

– e.g. cornybacteria on the skin produce fatty

acids- inhibit colonisation by pathogenic

bacteria

• They perform an essential metabolic

function

– e.g. digestion

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When good bugs turn bad

• The interaction between normal microbiota

and the host is mutually beneficial, and

dynamic

• They can under some circumstances

become pathogenic

• These are called opportunistic infections

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Opportunistic Infections

• Usually occur in a compromised host

– Weakened resistance

– Malnutrition

– Alcoholism

– Leukaemia

– HIV infection

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Innate vs Acquired Immunity

• Innate- acts quickly, recognises a broad range of pathogens, not specific, no memory

• Acquired (adaptive)- develops slowly after first exposure, rapidly on subsequent exposures, exquisitely specific, has memory

• These two “arms” are inextricably linked- the nature of the acquired response depends on the innate responses that are triggered

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Innate vs Adaptive Immunity

• Innate:

– Anatomic, physiologic, phagocytic,

inflammatory

– First line of defence

– Present before infection

– Recognise molecular classes, not pathogen-

specific

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Innate vs Adaptive Immunity

• Adaptive:

– Responds to antigenic challenge

– Delayed in response

– Exquisitely sensitive

– Cellular receptors

– Memory!

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Host Defences

3rd Line2nd Line1st Line

Inflammatory

response

Secretions

AntibodiesAntimicrobial

proteins

Mucous

membranes

LymphocytesPhagocytic

cells

Skin

SpecificNon-Specific

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Innate Immunity

• Skin: Low pH; mechanical barrier

• Mucous membranes: Normal flora; mucous entrapment; cilia

• Stomach: Low pH

• Chemicals: Lysozyme; interferons; complement; TLR’s;collectins

• Phagocytic cells: phagocytose and kill

• Inflammation: fluid leakage; serum proteins

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Innate Immunity

• Innate immunity relies on pattern

recognition

• Distinguishes self from non-self

• Examples are lysozyme, complement and

TLR’s

• Once recognised, a cell containing non-self

patterns may be phagocytosed

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Inflammation

• Tissue damage induces an inflammatory response

• May be triggered by (eg) a rusty nail, or infection

(LPS may trigger the response)

• Has several components:

– Vasodilation, increase in capillary permeability, influx

of phagocytes

• Requires chemical mediators: acute-phase

proteins, (brady)kinin, histidine etc

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Adaptive immunity

• Adaptive responses are restricted to specific

antigenic challenges

• Four main characteristics;

– Specificity

– Diversity

– Memory

– Self/non/self recognition

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Adaptive immunity

• Mediated by lymphocytes: B and T cells

• B lymphocytes: B cell receptor (Ab)

• T lymphocytes: T cell receptor

• Each receptor interacts with antigen

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B lymphocytes

• Mature in bone marrow

• Each carries a unique antigen-binding

receptor

• Receptor binds to antigen in its native state

• Cells divide and differentiate into plasma

cells (effector cells) or memory cells

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T lymphocytes

• Also produced in bone marrow, but are

“educated” in the thymus

• TCRs recognise antigen bound to MHC

molecules

• Two populations of T lymphocytes, Th

(helper) and Tc (cytotoxic). Also Ts

(suppressor) cells

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T cells

• Generally speaking:

• Th cells recognise antigen associated with

MHC Class II on antigen-presenting cells

• Tc cells recognise antigen associated with

MHC class I on infected cells

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Antigen presenting cells (APCs)

• Th cells are required to activate cellular and humoral immunity

• Th cells are activated by antigen presenting cells, via peptide/MHC classII

• Marcophages, B cells and dendritic cells are the primary APCs

• They express MHC class II, and co-stimulatory molecules (week 3)

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31T cells interacting with a macrophage

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Clonal Selection

• Each B cells has a specific receptor

• When antigen binds (and T cell help is

available) B cell proliferates

• B cell differentiates into plasma and

memory cells

• Similar selection occurs for T cells

• Amplifies antigen-specific cells

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